Destabilising microtubule polymerization regulates chondrocyte dedifferentiation and inflammation via nuclear factor kappa b and β-catenin pathway
Keywords:β-Catenin, Chondrocyte, Colchicine, COX-2, Osteoarthritis, Tubulin
The role of cell morphological changes in colchicine-inhibited tubulin polymerization of rabbit articular chondrocytes and their involvement in dedifferentiation were investigated. Colchicine treatment resulted in the dedifferentiation of chondrocytes, which was supported by the loss of type II collagen expression and proteoglycan production. Inhibition of tubulin de-polymerization with paclitaxel rescued colchicine-caused dedifferentiation and tubulin polymerization. Additionally, colchicine stimulated β-catenin overexpression, which is characterized by the accumulation of β-catenin into the cytosol determined by immunofluorescence staining. Inhibition of the β-catenin-mediated pathway by siR β-catenin recovered colchicine-caused the suppression of type II collagen expression in the chondrocytes. Treatment with colchicine also induced inflammation, as determined by the increased expression level of cyclooxygenase-2 and decreased IκB-α expression level by western blot analysis. Modulating the expression levels of pIκBα and IκBα via BMS 345541, was able to modulate colchicine-induced inflammatory effect.
Beier F. Cartilage Differentiation and the actin cytoskeleton: Cartilage. Springer, 2016, pp 253-67.
Chang SF, Huang KC, Lee KH, Chiang YC, Lee WR, Hsieh RZ, Su YP, Wu SC. Effects of visfatin on intracellular mechanics and catabolism in human primary chondrocytes through glycogen synthase kinase 3β inactivation. Int J Mol Sci. 2021; 22: 8107.
Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, Malaise M, de Seny D. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem Pharmacol. 2019; 165: 49-65.
Fernández-Torres J, Zamudio-Cuevas Y, López-Reyes A, Garrido-Rodríguez D, Martínez-Flores K, Lozada CA, Muñóz-Valle JF, Oregon-Romero E, Martínez-Nava GA. Gene-gene interactions of the Wnt/β-catenin signaling pathway in knee osteoarthritis. Mol Biol Rep. 2018: 45: 1089-98.
Ferrer MD, Busquets-Cortés C, Capo X, Tejada S, Tur JA, Pons A, Sureda A. Cyclooxygenase-2 inhibitors as a therapeutic target in inflammatory diseases. Curr Med Chem. 2019; 26: 3225-41.
Ghosh S, Scott AK, Seelbinder B, Barthold JE, Martin BMS, Kaonis S, Schneider SE, Henderson JT, Neu CP. Dedifferentiation alters chondrocyte nuclear mechanics during in vitro culture and expansion. Biophys J. 2022; 121: 131-41.
Goodson HV, Jonasson EM. Microtubules and microtubule-associated proteins. Cold Spring Harb Perspect Biol. 2018; 10: a022608.
Guo Q, Chen X, Chen J, Zheng G, Xie C, Wu H, Miao Z, Lin Y, Wang X, Gao W. STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway. Cell Death Dis. 2021; 12: 1-14.
Han Y, Kim SJ. Simvastatin-dependent actin cytoskeleton re-arrangement regulates differentiation via the extracellular signal-regulated kinase-1/2 and p38 kinase pathways in rabbit articular chondrocytes. Eur J Pharmacol. 2018; 834: 197-205.
Han Y, Yu SM, Shah FH, Kim SJ. Subversive molecular role of Krüppel-like factor 5 in extracellular matrix degradation and chondrocyte dedifferentiation. Funct Integr Genomics. 2022; 1-7.
Hodgkinson T, Kelly DC, Curtin CM, O’Brien FJ. Mechanosignalling in cartilage: an emerging target for the treatment of osteoarthritis. Nat Rev Rheumatol. 2022; 18: 67-84.
Huang P, Yan R, Zhang X, Wang L, Ke X, and Qu Y. Activating Wnt/β-catenin signaling pathway for disease therapy: Cha-llenges and opportunities. Pharmacol Ther. 2019; 196: 79-90.
Kim M, Song K, Jin EJ, Sonn J. Staurosporine and cytochalasin D induce chondrogenesis by regulation of actin dynamics in different way. Exp Mol Med. 2012; 44: 521-28.
Li H, Li L, Min J, Yang H, Xu X, Yuan Y, and Wang D. Levels of metalloproteinase (MMP-3, MMP-9), NF-kappaB ligand (RANKL), and nitric oxide (NO) in peripheral blood of osteoarthritis (OA) patients. Clin Lab. 2012; 58: 755-62.
Li SH, Wu QF. 2021. MicroRNAs target on cartilage extracellular matrix degradation of knee osteoarthritis. Eur Rev Med Pharmacol Sci. 25: 1185-97.
Li W, Xiong Y, Chen W, Wu L. Wnt/β‑catenin signaling may induce senescence of chondrocytes in osteoarthritis. Exp Ther Med. 2020; 20: 2631-38.
Lim HS, Jang Y, Moon BC, Park G. NF-κB signaling contributes to the inhibitory effects of Bombyx batryticatus on neuroinflammation caused by MPTP toxicity. Bangladesh J Pharmacol. 2021; 16: 96-102.
Liu XX, Zhu XY, Yu Z. Mulberrofuran G inhibits proliferation and migration by inactivating JAK2/STAT3 signaling in lung cancer cells. Bangladesh J Pharmacol. 2021; 16: 134-40.
Malkowski MG. The cyclooxygenases. Encycl Inorg Bioinorg Chem. 2011; 1-18.
Ostojic M, Zevrnja A, Vukojevic K, and Soljic V. Immunofluorescence analysis of NF-kB and iNOS expression in different cell populations during early and advanced knee osteoarthritis. Int J Mol Sci. 2021; 22: 6461.
Pannunzio A, Coluccia M. Cyclooxygenase-1 (COX-1) and COX-1 inhibitors in cancer: A review of oncology and medicinal chemistry literature. Pharmaceuticals 2018; 11: 101.
Shah FH, Kim SJ. Therapeutic role of medicinal plant extracts and bioactive compounds in osteoarthritis. Adv Tradit Med. 2022, 1-8.
Shen S, Hou Y, Wu Y. Tongxinluo preserves the renal function in diabetic kidney disease via protecting the HK-2 cells from the patterns of programmed cell death. Bangladesh J Pharmacol. 2021; 16: 52-64.
Shi Y, Hu X, Cheng J, Zhang X, Zhao F, Shi W, Ren B, Yu H, Yang P, Li Z. A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development. Nat Commun. 2019; 10: 1-14.
Sun Y, Leng P, Li D, Gao H, Li Z, Li C, Zhang H. Mechanism of abnormal chondrocyte proliferation induced by Piezo1-siRNA exposed to mechanical stretch. Biomed Res Int. 2020: 2020.
Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and prostaglandins in tumor immunology and micro-environment of gastrointestinal cancer. Gastroenterology. 2021; 161: 1813-29.
Whittaker JL, Runhaar J, Bierma-Zeinstra S, Roos EM. A life-span approach to osteoarthritis prevention. Osteoarthr Cartil. 2021; 29: 1638–1653.
Xiao Y, Liu L, Zheng Y, Liu W, Xu Y. Kaempferol attenuates the effects of XIST/miR-130a/STAT3 on inflammation and extracellular matrix degradation in osteoarthritis. Future Med Chem. 2021; 13: 1451-64.
Yu SM, Han Y, Kim SJ. Simvastatin induces differentiation in rabbit articular chondrocytes via Wnt/β-catenin pathway. Eur J Pharmacol. 2019; 863: 172672.
Yu SM, Kim S. Retinoic acid potentiates nitric oxide-induced dedifferentiation through the ERK pathway in rabbit articular chondrocytes. J Life Sci. 2011; 21: 534-41.
Zhang T, Ma C, Zhang Z, Zhang H, Hu H. NF‐κB signaling in inflammation and cancer. Med Comm. 2021; 2: 618-53.
Zheng L, Zhang Z, Sheng P, Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev. 2021; 66: 101249.
How to Cite
Copyright (c) 2023 Yohan Han, Young Seok Eom, Fahad Hassan Shah, Song Ja Kim
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).